Markers for the identification of late breast cancer recurrence

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Selenium in serum and neoplastic tissue in breast cancer: correlation with CEA

Trace element selenium (Se) is regarded to be a breast cancer preventive factor involved in multiple protective pathways. In all, 80 women with breast cancer who underwent a radical mastectomy were enrolled in the study. Serum Se and carcinoembryonic antigen levels were measured using a fluorometric and IRMA assay, respectively. Se tissue concentration was determined by a tissue extracting fluorometric assay. For statistical analysis purposes t-test was used and P-values <0.001 were regarded as statistically significant. Serum Se was 42.5±7.5 μg l−1 in breast cancer patients and 67.6±5.36 μg l−1 in the age-matched control group of healthy individuals. Serum carcinoembryonic antigen in patients was 10±1.7 U ml−1 (normal <2.5 U ml−1 in nonsmokers/<3.5 U ml−1 in smokers). A statistically significant difference was found for both serum Se and CEA between two groups studied (P<0.001). Neoplastic tissue Se concentration was 2660±210 mg g−1 tissue; its concentration in the adjacent non-neoplastic tissue was 680±110 mg g−1 tissue (P<0.001). An inverse relationship between Se and CEA serum levels was found in the two groups studied (r=−0.794). There was no correlation between serum/tissue Se concentration and stage of the disease. The decrease in serum Se concentration as well as its increased concentration in the neoplastic breast tissue is of great significance. These alterations may reflect part of the defence mechanisms against the carcinogenetic process

CTCs-derived xenograft development in a Triple Negative breast cancer case

Triple-negative breast cancer (TNBC) is characterized by high rates of metastasis and no available molecular targets. CTCs derived xenografts (CDX) have demonstrated to be a promising tool for understanding cancer biology. In our study, a CDX from a TNBC patient was developed for the first time. After CDX characterization, WNT signaling was found as the main mechanism related with this tumor biology and potential CTCs markers were identified and subsequently validated in TNBC patients. In this cohort high levels of MELK expression were associated with poorer survival rates. Overall, our study demonstrates that CTCs from TNBC are tumorigenic and CDXs are a useful model to obtain valuable information about the tumor

Enhanced prediction of breast cancer prognosis by evaluating expression of p53 and prostate-specific antigen in combination

p53 gene mutation is the most common genetic alteration in neoplastic diseases, including breast cancer, for which p53 alteration may indicate poor prognosis. Recent clinical evidence suggests that prostate-specific antigen (PSA) expression may identify breast cancer patients with favourable outcome. Assessment of p53 and PSA in combination, potentially offering improved prediction, has not yet been performed. Extracts from 952 primary breast carcinomas were assayed for PSA and p53 by quantitative enzyme-linked immunosorbent assays (ELISAs) developed by the authors. Concentrations of each marker were classified as negative or positive on the basis of median and 30th percentile cut-off points for p53 and PSA respectively. Patients followed for a median of 6 years having different combinations of negative or positive status for PSA and p53 were compared with respect to the relative risks (RRs) for relapse and death by Cox proportional hazards regression analysis, in which an interaction term was also evaluated, and with respect to disease-free survival (DFS) and overall survival (OS) probabilities by Kaplan–Meier plots and log-rank tests. Multivariate models were adjusted for oestrogen and progesterone receptor status, nodal status, patient age, tumour size, DNA ploidy, S phase fraction and receipt of chemotherapy. Interactions were not found between the status of PSA and p53 in the Cox models, in which PSA-negativity (RR = 1.47, P = 0.020 for DFS, and RR = 1.49, P = 0.023 for OS) and p53-positivity (RR = 1.46, P = 0.017 for DFS, and RR = 1.41, P = 0.033 for OS) were individually associated with prognosis. Evaluation of a combined three-level variable revealed that PSA(–)/p53(+) patients had significantly higher risks for relapse (RR = 2.13, P < 0.001) and death (RR = 2.08, P = 0.001) than PSA(+)/p53(–) patients, and that patients positive or negative for both markers had intermediate risks for the outcome events in the same multivariate analysis (RR = 1.45 for both DFS and OS). The results of our study demonstrate that the assessment of combined PSA and p53 expression status by ELISAs, easily applicable to breast tumour extracts prepared for steroid hormone receptor analyses, may stratify breast cancer patients into groups differing by relapse and death risks of greater magnitude than offered by the assessment of either p53 or PSA alone. © 1999 Cancer Research Campaig

Development of a quantitative luminometric hybridization assay for the determination of telomerase activity

Objectives: To develop a quantitative luminometric hybridization assay for the determination of telomerase activity in tissue and eel extracts. Design and Methods: Quantification is based on the coamplification of telomeric repeats synthesized by telomerase along with a specifically designed recombinant DNA-internal standard (DNA-LS). The DNA-IS has a similar size and the same primer recognition sites as the telomerase DNA products and differs from them only in a central 18 bp sequence. PCR products are captured on microtiter wells via the biotin-streptavidin system and hybridized with two distinct digoxigenin-labeled oligonucleotide probes that are designed to recognize specifically telomerase products and DNA-IS. The hybrids are quantified by a luminometric reaction using an antidigoxigenin antibody conjugated to alkaline phosphatase. The hybridization assay was validated with the MCF-7 breast carcinoma and leukemia K-562 cell lines and a synthetic telomerase product (R-8), Results: Luminescence ratios for telomerase products and DNA-IS were linearly related to the concentration of the pre-PCR product synthesized by telomerase (R-8), in the range of 0.0005 to 10 pM. The overall reproducibility of the assay (between-run) varied between 11.3 and 15%. Application of the method in eleven breast tumors showed a great variation in the levels of telomerase enzymatic activity. Conclusions: The proposed luminometric hybridization assay for the quantitative determination of telomerase enzymatic activity is highly sensitive and can be used for a large-scale prospective evaluation of clinical samples. (C) 2001 The Canadian Society of Clinical Chemists. All rights reserved

miRNA-21 as a novel therapeutic target in lung cancer

Athina Markou, Martha Zavridou, Evi S LianidouAnalysis of Circulating Tumor Cells, Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Athens, GreeceAbstract: Lung cancer is a leading cause of cancer death, and late diagnosis is one of the most important reasons for the high mortality rate. microRNAs (miRNAs) are key players in gene regulation and therefore in tumorigenesis. As far as lung carcinogenesis is concerned, miRNAs open novel fields in biomarker research, in diagnosis, and in therapy. In this review we focus on miR-21 in lung cancer and especially on how miR-21 is involved 1) as a biomarker in response or resistance to therapy or 2) as a therapeutic target.Keywords: lung cancer, miR-21, therapeutic target, NSCLC, response to therap